There is increasing evidence that the intensity and specificity of immune responses are largely determined by cell-cell interactions that suppress or activate both cellular immunity and antibody production. Different regulatory functions, for example helper or suppressor activity, had been assigned to T-cell sets which each express a characteristic pattern of "marker" glycoproteins at their cell membrane. Nonetheless, the molecular basis of these specific T-cell functions are not known. Nor do we understand the initial interaction between lymphocytes and antigen-presenting cells that probably determine the types of T-cells that are activated. This is not surprising, since real insight into these interactions are not possible without a description of the receptors on different sets of T-cells. These basic questions must be answered in order to arrive at a working explanation of more complex phenomena such as the role and function of immune response genes, the development of neonatal and adult tolerance, and the autoimmune syndromes. Many of these questions have been difficult to answer because of technical reasons. A biochemical explanation of the function and specificity of antibodies has come from analyses of large amounts of homogeneous immunoglobulins produced by myelomas. Analysis of antibody formation can be quantitated by highly sensitive and precise radioimmunoassays; antibody-forming cells can be enumerated using various hemolytic plaque techniques. Although the ultimate goal of this project is to obtain a molecular explanation for the development of unresponsiveness to antigens present on an individual's own tissues, definition of the structure and function of antigen-specific molecules that suppress or activate immune responses represents an essential step toward this goal. The approach we have taken is based upon (a) the definition of culture conditions permitting clonal growth of T-cells and macrophages that are specialized to mediate different immunologic functions and (b) the development of serologic reagents that bind specifically to molecules secreted by T-suppressor cells.